I am interested in the chromatin accessibility of cancer cells, in particular any differences between clones. We plan to perform scATAC-seq (perhaps scRNA-seq as well).
However, I am worried that the copy number alterations may affect the peak calling. This is especially relevant when my interest is in clonal heterogeneity, where I would need to disentangle between an altered copy number VS altered chromatin accessibility.
I've seen an answer for normalizing ChIP-seq data before, which suggested to call CNV from input control data, and remove these regions from analysis. However, I don't think input control is available for scATAC-seq.
My questions are:
- Is my worry legit?
- Are there any ways to normalize the ATAC-seq data by copy number?
- If yes, can it be done by inferred copy number changes from scATAC-seq / scRNA-seq data? I've seen a couple preprints / published articles, but not sure which methods should be used / if they are reliable.
Thanks in advance for any input / discussion.
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